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单一组分、自组装的蛋白纳米颗粒展示了受体结合域和稳定的刺突，作为 SARS-CoV-2 的疫苗候选物。

Single-component, self-assembling, protein nanoparticles presenting the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates.

机构信息

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA 19140, USA.

出版信息

Sci Adv. 2021 Mar 19;7(12). doi: 10.1126/sciadv.abf1591. Print 2021 Mar.

DOI:10.1126/sciadv.abf1591
PMID:33741598
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7978432/
Abstract

Vaccination against SARS-CoV-2 provides an effective tool to combat the COVID-19 pandemic. Here, we combined antigen optimization and nanoparticle display to develop vaccine candidates for SARS-CoV-2. We first displayed the receptor-binding domain (RBD) on three self-assembling protein nanoparticle (SApNP) platforms using the SpyTag/SpyCatcher system. We then identified heptad repeat 2 (HR2) in S2 as the cause of spike metastability, designed an HR2-deleted glycine-capped spike (S2GΔHR2), and displayed S2GΔHR2 on SApNPs. An antibody column specific for the RBD enabled tag-free vaccine purification. In mice, the 24-meric RBD-ferritin SApNP elicited a more potent neutralizing antibody (NAb) response than the RBD alone and the spike with two stabilizing proline mutations in S2 (S2P). S2GΔHR2 elicited twofold higher NAb titers than S2P, while S2GΔHR2 SApNPs derived from multilayered E2p and I3-01v9 60-mers elicited up to 10-fold higher NAb titers. The S2GΔHR2-presenting I3-01v9 SApNP also induced critically needed T cell immunity, thereby providing a promising vaccine candidate.

摘要

针对 SARS-CoV-2 的疫苗接种提供了一种对抗 COVID-19 大流行的有效工具。在这里，我们结合抗原优化和纳米颗粒展示来开发针对 SARS-CoV-2 的疫苗候选物。我们首先使用 SpyTag/SpyCatcher 系统将受体结合域 (RBD) 展示在三个自组装蛋白纳米颗粒 (SApNP) 平台上。然后，我们确定 S2 中的七肽重复 2 (HR2) 是 Spike 亚稳定性的原因，设计了 HR2 缺失的甘氨酸封端的 Spike (S2GΔHR2)，并将 S2GΔHR2 展示在 SApNPs 上。针对 RBD 的抗体柱可实现无标签疫苗纯化。在小鼠中，24 聚体 RBD-铁蛋白 SApNP 引发的中和抗体 (NAb) 反应比单独的 RBD 和 S2 中具有两个稳定脯氨酸突变的 Spike (S2P) 更强。S2GΔHR2 引发的 NAb 滴度比 S2P 高两倍，而源自多层 E2p 和 I3-01v9 60 聚体的 S2GΔHR2 SApNPs 引发的 NAb 滴度高达 10 倍。展示 S2GΔHR2 的 I3-01v9 SApNP 还诱导了急需的 T 细胞免疫，从而提供了一种有前途的疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/7978432/01173b35c34d/abf1591-F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/7978432/95b33f28a4da/abf1591-F1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/7978432/9ceb1a8bd84a/abf1591-F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/7978432/accba4eef08d/abf1591-F4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/7978432/01173b35c34d/abf1591-F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/7978432/95b33f28a4da/abf1591-F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/7978432/82b5c3d78985/abf1591-F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/7978432/9ceb1a8bd84a/abf1591-F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/7978432/accba4eef08d/abf1591-F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/7978432/ff3a8c37050c/abf1591-F5.jpg
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